The present invention relates to a series of thiazolidine derivatives which are characterised by the presence, inter alia, of a quitone group in their molecules. These compounds have valuable therapeutic and prophylactic activities, including anti-diabetic activities, and the invention therefore also provides methods and compositions using these compounds for the treatment and prophylaxis of diabetes and diabetic complications, as described in greater detail hereafter. The invention also provides processes for preparing these novel compounds.
A number of compounds in which a substituted alkoxy-benzyl group is attached to the 5-position of a thiazolidine-2,4-dione group is known. These compounds can be generally represented by the formula (A): ##STR2##
For example, European Patent Publication No. 8 203 discloses a series of compounds of the type shown in formula (A) in which R.sup.a may be an alkyl or cycloalkyl group. European Patent Publication No. 139 421 discloses such compounds in which the group equivalent to R.sup.a in formula (A) above is a chroman or similar group, and Y. Kawamatsu et al. [Chem. Pharm. Bull., 30, 3580-3600 (1982)] disclose a wide range of such compounds of formula (A) in which R.sup.a may be various phenyl, substituted phenyl, alkylamino, cycloalkyl, terpenyl and heterocyclic groups.
All of the prior thiazolidine derivatives referred to above are said to have the ability to lower blood glucose levels, and it is thought that this is achieved by reducing insulin resistance in the peripheral system.
However, it is currently thought that the compounds of the prior art which are closest to those of the present invention are disclosed in European Patent Publication No. 441 605, assigned to the present assignees, as these, like the compounds of the present invention may contain a quinone group, although attached in a different manner to the alkylene group of formula --(CH.sub.2).sub.n --.
We have now discovered a series of novel compounds which, in addition to the ability to reduce insulin resistance in the peripheral tissues (which is the sole basis of the antidiabetic activity of most of the prior art compounds) also exhibits other activities, for example, like the compounds of European Patent Publication No. 441 605, the present compounds have the ability to suppress hepatic gluconeogenesis in the liver, which is one of the causes of diabetes. These additional activities, combined with a low toxicity, mean that the compounds of the present invention will be more effective than the prior art compounds and able to treat a wider range of disorders. The compounds of the present invention have been surprisingly found to have a substantially better activity than do the compounds of prior art European Patent Publication No. 441 605.